crossing96/oncoscreening huggingface dataset:
Urachal rhabdomyosarcoma in childhood: a rare entity with a poor outcome.	"BACKGROUND/PURPOSE: Rhabdomyosarcoma (RMS) of the urachus is rare and gathered in the ""abdominal and other locations"" group for oncological treatment purpose, and therefore not well characterized. Our aim was to assess the clinical and prognostic specific features of urachal primary RMS in childhood. METHODS: We retrospectively reviewed the charts of 8 patients with an urachal RMS treated between 1984 and 2013 in two Pediatric Oncology Departments. Median follow-up was 42 months (18-100). RESULTS: Urachal RMSs were embryonal in 6, alveolar in 1, and not otherwise specified in 1. Age at diagnosis was 4.4 years (2.6-6). All patients had advanced locoregional extension (IRS IIIIV) and 1 had distant metastasis. All had chemotherapy and surgical resection. Six had external radiotherapy. Four had extensive peritoneal recurrence including 2 with distant metastasis, within a median of 25 months (11-82) after the end of treatment. One had metastatic progression under primary treatment. Four of them died between 18 and 57 months after diagnosis, and 1 is still under treatment for a late recurrence. Only 3 are free of disease after 3.3 to 7.9 years of follow-up. CONCLUSIONS: Pediatric urachal cancer is rare and poorly identified. In our series, RMS was exclusive in this location. Locoregional extension was always advanced. Prognosis was poor despite current multimodal therapy. We underline the need for new therapeutical strategies."	bladder
Prognostic and predictive value of epigenetic biomarkers and clinical factors in upper tract urothelial carcinoma.	AIM: We conducted this study to identify gene promoter methylation status and clinical predictors for upper tract urothelial carcinoma (UTUC) patients. MATERIALS & METHODS: Using methylation-sensitive PCR, we examined ten genes promoter methylation status in 687 UTUC patients. RESULTS: A methylated promoter of three genes to predict higher tumor stage (T3 and T4), five genes to predict higher tumor grade (G3) and one gene to predict pN+ were certified in this study. Nine factors were significantly associated with poor cancer-specific survival. Six factors were considered as predictors to develop bladder recurrence after surgery. CONCLUSION: Methylation occurs commonly in UTUCs, may affect carcinogenic mechanisms, and is a well predictive factor for cancer-specific survival and bladder recurrence in UTUCs.	bladder
Loss of FOXA1 Drives Sexually Dimorphic Changes in Urothelial Differentiation and Is an Independent Predictor of Poor Prognosis in Bladder Cancer.	We previously found loss of forkhead box A1 (FOXA1) expression to be associated with aggressive urothelial carcinoma of the bladder, as well as increased tumor proliferation and invasion. These initial findings were substantiated by The Cancer Genome Atlas, which identified FOXA1 mutations in a subset of bladder cancers. However, the prognostic significance of FOXA1 inactivation and the effect of FOXA1 loss on urothelial differentiation remain unknown. Application of a univariate analysis (log-rank) and a multivariate Cox proportional hazards regression model revealed that loss of FOXA1 expression is an independent predictor of decreased overall survival. An ubiquitin Cre-driven system ablating Foxa1 expression in urothelium of adult mice resulted in sex-specific histologic alterations, with male mice developing urothelial hyperplasia and female mice developing keratinizing squamous metaplasia. Microarray analysis confirmed these findings and revealed a significant increase in cytokeratin 14 expression in the urothelium of the female Foxa1 knockout mouse and an increase in the expression of a number of genes normally associated with keratinocyte differentiation. IHC confirmed increased cytokeratin 14 expression in female bladders and additionally revealed enrichment of cytokeratin 14-positive basal cells in the hyperplastic urothelial mucosa in male Foxa1 knockout mice. Analysis of human tumor specimens confirmed a significant relationship between loss of FOXA1 and increased cytokeratin 14 expression.	bladder
Competing risks data analysis with high-dimensional covariates: an application in bladder cancer.	Analysis of microarray data is associated with the methodological problems of high dimension and small sample size. Various methods have been used for variable selection in high-dimension and small sample size cases with a single survival endpoint. However, little effort has been directed toward addressing competing risks where there is more than one failure risks. This study compared three typical variable selection techniques including Lasso, elastic net, and likelihood-based boosting for high-dimensional time-to-event data with competing risks. The performance of these methods was evaluated via a simulation study by analyzing a real dataset related to bladder cancer patients using time-dependent receiver operator characteristic (ROC) curve and bootstrap .632+ prediction error curves. The elastic net penalization method was shown to outperform Lasso and boosting. Based on the elastic net, 33 genes out of 1381 genes related to bladder cancer were selected. By fitting to the Fine and Gray model, eight genes were highly significant (P<0.001). Among them, expression of RTN4, SON, IGF1R, SNRPE, PTGR1, PLEK, and ETFDH was associated with a decrease in survival time, whereas SMARCAD1 expression was associated with an increase in survival time. This study indicates that the elastic net has a higher capacity than the Lasso and boosting for the prediction of survival time in bladder cancer patients. Moreover, genes selected by all methods improved the predictive power of the model based on only clinical variables, indicating the value of information contained in the microarray features.	bladder
High Coexpression of Runt-related Transcription Factor 2 (RUNX2) and p53 Independently Predicts Early Tumor Recurrence in Bladder Urothelial Carcinoma Patients.	Conventional prognostic factors for bladder cancer are inadequate to predict tumor recurrence and/or progression successfully; thus, the identification of adjunctive novel prognostic biomarkers is of paramount importance. In this study, the immunohistochemical expression patterns and clinical significance of RUNX2, WWOX, and p53 were investigated in a tissue microarray of 87 primary urothelial carcinomas and 17 control cases. We found that RUNX2, WWOX, and p53 were significantly correlated and overexpressed in urothelial carcinoma cases compared with the control group. RUNX2 and p53 were significantly upregulated in association with high-grade, nonpapillary pattern, and bilharziasis. Muscle-invasive tumors significantly overexpressed RUNX2. WWOX overexpression was significantly associated with high-grade tumors and inversely correlated with age. In a bivariate analysis, the risk of early tumor recurrence and progression was significantly associated with RUNX2 and p53 overexpression and bilharziasis. A multivariate Cox regression analysis proved that RUNX2 and p53 were independent predictors of early tumor recurrence. The ROC curve analysis showed that combined RUNX2 and p53 high expression (scores >3 and >5, respectively) had the highest accuracy (73.6%) for the prediction of early tumor recurrence. We conclude that RUNX2 and p53 might be functionally related and are likely involved in bladder tumor carcinogenesis and aggressiveness, which provides a new perspective for targeted therapy. RUNX2 and p53 independently predict early tumor recurrence in bladder carcinoma patients, with the highest prediction accuracy being achieved on their combined high expression. The role of WWOX in bladder urothelial carcinoma and its relationship with RUNX2 and p53 remains unclear and warrants further investigation.	bladder
Mitochondrial DNA Content as Risk Factor for Bladder Cancer and Its Association with Mitochondrial DNA Polymorphisms.	Mitochondrial DNA (mtDNA) content has been shown to be associated with cancer susceptibility. We identified 926 bladder cancer patients and compared these with 926 healthy controls frequency matched on age, gender, and ethnicity. Patients diagnosed with bladder cancer had significantly decreased mtDNA content when compared with control subjects (median, 0.98 vs. 1.04, P < 0.001). Low mtDNA content (i.e., less than the median in control subjects) was associated with a statistically significant increased risk of bladder cancer, when compared with high mtDNA content [Odds ratio (OR), 1.37; 95% confidence interval (CI), 1.13-1.66; P < 0.001). In a trend analysis, a statistically significant dose-response relationship was detected between lower mtDNA content and increasing risk of bladder cancer (Ptrend <0.001). When stratified by host characteristics, advanced age (>65 years), male sex and positive smoking history were significantly associated with low mtDNA content and increased risk of bladder cancer. We identified two unique mtDNA polymorphisms significantly associated with risk of bladder cancer: mitot10464c (OR, 1.39; 95% CI, 1.00-1.93; P = 0.048) and mitoa4918g (OR, 1.40; 95% CI, 1.00-1.95; P = 0.049). Analysis of the joint effect of low mtDNA content and unfavorable mtDNA polymorphisms revealed a 2.5-fold increased risk of bladder cancer (OR, 2.50; 95% CI, 1.60-3.94; P < 0.001). Significant interaction was observed between mitoa4918g and mtDNA content (Pinteraction = 0.028). Low mtDNA content was associated with increased risk of bladder cancer and we identified new susceptibility mtDNA alleles associated with increased risk that require further investigation into the biologic underpinnings of bladder carcinogenesis.	bladder
Loss of e-cadherin and retinoblastoma genes in a case of urothelial carcinoma with scrotal metastasis.	Cutaneous metastases from urologic cancers are very uncommon, usually represent widespread metastatic disease and are associated with a very poor prognosis. They may occur in 1% of patients with urologic malignancies, most commonly from kidney, followed by bladder and prostate tumors. In this report, we describe a case of urothelial carcinoma with metastases to the scrotum treated with platinum based chemotherapy with a durable complete response lasting more than 14 months. Molecular profiling revealed deleterious mutations in e-cadherin and retinoblastoma genes, suggesting their possible role in the pathogenesis of cutaneous metastases. Further studies are needed to validate this observation.	bladder
Mir-135a enhances cellular proliferation through post-transcriptionally regulating PHLPP2 and FOXO1 in human bladder cancer.	BACKGROUND: Bladder cancer is the most common malignancy in urinary system and the ninth most common malignancy in the world. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression by targeted repression of transcription and translation and play essential roles during cancer development. We investigated the expression of miR-135a in bladder cancer and explored its bio-function during bladder cancer progression. METHODS: The expression of miR-135a in bladder cancer cells and tissues are performed by using Real-time PCR assay. Cell viability assay (MTT assay), colony formation assay, anchorage-independent growth ability assay and Bromodeoxyuridine labeling and immunofluorescence (BrdUrd) assay are used to examine cell proliferative capacity and tumorigenicity. Flow cytometry analysis is used to determine cell cycle progression. The expressions of p21, p27, CyclinD1, Ki67, PHLPP2 and FOXO1 are measured by Western blotting assay. Luciferase assay is used to confirm whether FOXO1 is the direct target of miR-135a. RESULTS: miR-135a is upregulated in bladder cancer cells and tissues. Enforced expression of miR-135a promotes bladder cancer cells proliferation, whereas inhibition of miR-135a reverses the function. Furthermore, for the first time we demonstrated PHLPP2 and FOXO1 are direct targets of miR-135a and transcriptionally down-regulated by miR-135a. Suppression of PHLPP2 or FOXO1 by miR-135a, consisted with dysregulation of p21, p27, Cyclin D1 and Ki67, play important roles in bladder cancer progression. CONCLUSION: Our study demonstrates that miR-135a promotes cell proliferation in bladder cancer by targeting PHLPP2 and FOXO1, and is performed as an onco-miR.	bladder
Ras induces experimental lung metastasis through up-regulation of RbAp46 to suppress RECK promoter activity.	"BACKGROUND: Mutant Ras plays multiple functions in tumorigenesis including tumor formation and metastasis. Reversion-inducing cysteine-rich protein with Kazal motifs (RECK), a metastasis inhibitor gene, suppresses matrix metalloproteinase (MMP) activity in the metastatic cascade. Clarifying the relationship between Ras and RECK and understanding the underlying molecular mechanism may lead to the development of better treatment for Ras-related tumors. METHODS: Suppression subtractive hybridization PCR (SSH PCR) was conducted to identify Ha-ras (val12) up-regulated genes in bladder cancer cells. Stable cell lines of human breast cancer (MCF-7-ras) and mouse NIH3T3 fibroblasts (7-4) harboring the inducible Ha-ras (val12) oncogene, which could be induced by isopropylthio-β-D-galactoside (IPTG), were used to clarify the relationship between Ras and the up-regulated genes. Chromatin immunoprecipitation (ChIP) assay, DNA affinity precipitation assay (DAPA) and RECK reporter gene assay were utilized to confirm the complex formation and binding with promoters. RESULTS: Retinoblastoma binding protein-7 (RbAp46) was identified and confirmed as a Ha-ras (val12) up-regulated gene. RbAp46 could bind with histone deacetylase (HDAC1) and Sp1, followed by binding to RECK promoter at the Sp1 site resulting in repression of RECK expression. High expression of Ras protein accompanied with high RbAp46 and low RECK expression were detected in 75% (3/4) of the clinical bladder cancer tumor tissues compared to the adjacent normal parts. Ras induced RbAp46 expression increases invasion of the bladder cancer T24 cells and MMP-9 activity was increased, which was confirmed by specific lentiviral shRNAs inhibitors against Ras and RbAp46. Similarly, knockdown of RbAp46 expression in the stable NIH3T3 cells ""7-4"" by shRNA decreased Ras-related lung metastasis using a xenograft nude mice model. CONCLUSIONS: We confirmed that RbAp46 is a Ha-ras (val12) up-regulated gene and binds with HDAC1 and Sp1. Furthermore, RbAp46 binds to the RECK promoter at the Sp1 site via recruitment by Sp1. RECK is subsequently activated, leading to increased MMP9 activity, which may lead to increased metastasis in vivo. Our findings of Ras upregulation of RbAp46 may lead to revealing a novel mechanism of Ras-related tumor cell metastasis."	bladder
Novel biomarkers to predict response and prognosis in localized bladder cancer.	This review summarizes recent developments in diagnostic and prognostic biomarkers for nonmuscle invasive bladder cancer (NMIBC). Although the number of new biomarkers increases continuously, none are included in practice guidelines. Most NMIBC biomarkers show a higher sensitivity than urinary cytology, but lower specificity. Some protein and chromosome markers have been approved for screening and follow-up of patients in combination with cystoscopy. The long interval required for validation, testing, and approval of the assays and the lack of standardization could explain present issues in biomarker research. To enhance the development of new biomarkers, a more structured approach is required.	bladder
Neoadjuvant therapy in muscle-invasive bladder cancer: a model for rational accelerated drug development.	Since the advent of cisplatin-based combination therapy in the management of muscle-invasive and advanced bladder cancer, there has been little progress in improving outcomes for patients. Novel therapies beyond cytotoxic chemotherapy are needed. The neoadjuvant paradigm lends to acquiring ample pretreatment and posttreatment tumor tissue as a standard of care, which enables comprehensive biomarker analyses to better understand mechanisms of both response and resistance, which will aid drug development. This article discusses the evolution of neoadjuvant therapy as standard treatment and the role it may serve toward the development of novel therapies.	bladder
Neoadjuvant chemotherapy in the management of muscle-invasive bladder cancer: bridging the gap between evidence and practice.	Although cisplatin-based chemotherapy followed by radical cystectomy is the standard treatment of muscle-invasive bladder cancer, population-based studies reveal that only a small fraction of patients actually receive such treatment. A comprehensive understanding of the reasons for this gap between efficacy and effectiveness is necessary to increase the likelihood of cure of all patients with muscle-invasive bladder cancer. These reasons include systems-, provider-, and patient-level barriers that are not amenable to a single solution. Tackling each barrier will ultimately be necessary to bridge the disconnect between what is achievable and what is actually achieved.	bladder
The prognostic impact of perioperative blood transfusion on survival in patients with bladder urothelial carcinoma treated with radical cystectomy.	PURPOSE: The aim of our study was to assess the influence of perioperative blood transfusion (PBT) on survival outcomes following radical cystectomy (RC) and pelvic lymph node dissection (PLND). MATERIALS AND METHODS: We reviewed and analyzed the clinical data of 432 patients who underwent RC for bladder cancer from 1991 to 2012. PBT was defined as the transfusion of allogeneic red blood cells during RC or postoperative hospitalization. RESULTS: Of all patients, 315 patients (72.9%) received PBT. On multivariate logistic regression analysis, female gender (p=0.015), a lower preoperative hemoglobin level (p=0.003), estimated blood loss>800 mL (p<0.001), and performance of neoadjuvant chemotherapy (p<0.001) were independent risk factors related to requiring perioperative transfusions. The receipt of PBT was associated with increased overall mortality (hazard ratio, 1.91; 95% confidence interval, 1.25-2.94; p=0.003) on univariate analysis, but its association was not confirmed by multivariate analysis (p=0.058). In transfused patients, a transfusion of >4 packed red blood cell units was an independent predictor of overall survival (p=0.007), but not in cancer specific survival. CONCLUSIONS: Our study was not conclusive to detect a clear association between PBT and survival after RC. However, the efforts should be made to continue limiting the overuse of transfusion especially in patients who are expected to have a high probability of PBT, such as females and those with a low preoperative hemoglobin level and history of neoadjuvant chemotherapy.	bladder
Variability in surgical quality in a phase III clinical trial of radical cystectomy in patients with organ-confined, node-negative urothelial carcinoma of the bladder.	BACKGROUND AND OBJECTIVES: Previous studies have shown that variability in surgical technique can affect the outcomes of cooperative group trials. We analyzed measures of surgical quality and clinical outcomes in patients enrolled in the p53-MVAC trial. METHODS: We performed a post-hoc analysis of patients with pT1-T2N0M0 urothelial carcinoma of the bladder following radical cystectomy (RC) and bilateral pelvic and iliac lymphadenectomy (LND). Measures of surgical quality were examined for associations with time to recurrence (TTR) and overall survival (OS). RESULTS: We reviewed operative and/or pathology reports for 440 patients from 35 sites. We found that only 31% of patients met all suggested trial eligibility criteria of having ≥15 lymph nodes identified in the pathologic specimen (LN#) and having undergone both extended and presacral LND. There was no association between extent of LND, LN#, or presacral LND and TTR or OS after adjustment for confounders and multiple testing. CONCLUSIONS: We demonstrated that there was substantial variability in surgical technique within a cooperative group trial. Despite explicit entry criteria, many patients did not undergo per-protocol LNDs. While outcomes were not apparently affected, it is nonetheless evident that careful attention to study design and quality monitoring will be critical to successful future trials.	bladder
Comparative effectiveness of gemcitabine plus cisplatin versus methotrexate, vinblastine, doxorubicin, plus cisplatin as neoadjuvant therapy for muscle-invasive bladder cancer.	BACKGROUND: Gemcitabine plus cisplatin (GC) has been adopted as a neoadjuvant regimen for muscle-invasive bladder cancer despite the lack of Level I evidence in this setting. METHODS: Data were collected using an electronic data-capture platform from 28 international centers. Eligible patients had clinical T-classification 2 (cT2) through cT4aN0M0 urothelial cancer of the bladder and received neoadjuvant GC or methotrexate, vinblastine, doxorubicin, plus cisplatin (MVAC) before undergoing cystectomy. Logistic regression was used to compute propensity scores as the predicted probabilities of patients being assigned to MVAC versus GC given their baseline characteristics. These propensity scores were then included in a new logistic regression model to estimate an adjusted odds ratio comparing the odds of attaining a pathologic complete response (pCR) between patients who received MVAC and those who received GC. RESULTS: In total, 212 patients (146 patients in the GC cohort and 66 patients in the MVAC cohort) met criteria for inclusion in the analysis. The majority of patients in the MVAC cohort (77%) received dose-dense MVAC. The median age of patients was 63 years, they were predominantly men (74%), and they received a median of 3 cycles of neoadjuvant chemotherapy. The pCR rate was 29% in the MVAC cohort and 31% in the GC cohort. There was no significant difference in the pCR rate when adjusted for propensity scores between the 2 regimens (odds ratio, 0.91; 95% confidence interval, 0.48-1.72; P = .77). In an exploratory analysis evaluating survival, the hazard ratio comparing hazard rates for MVAC versus GC adjusted for propensity scores was not statistically significant (hazard ratio, 0.78; 95% confidence interval, 0.40-1.54; P = .48). CONCLUSIONS: Patients who received neoadjuvant GC and MVAC achieved comparable pCR rates in the current analysis, providing evidence to support what has become routine practice.	bladder
A Case of High-grade Transitional Cell Carcinoma of the Bladder in a Pediatric Patient With Turner Syndrome.	Transitional cell carcinoma is a rare entity in children, especially in the first decade of life. The majority of these tumors are of low grade and noninvasive. We report an interesting case of a high-grade superficial transitional cell carcinoma in a 3-year-old girl with Turner syndrome.	bladder